Objective To examine the relationship between depression,
treatment of depression, and interferon gamma (IFN-gamma) production by
peripheral blood mononuclear cells in patients with comorbid diagnoses of
relapsing-remitting multiple sclerosis (MS) and major depressive disorder.

Design A randomized comparative outcome trial of three
16-week treatments for depression. Assessments were conducted at baseline, week
8, and treatment cessation.

Setting An academic outpatient treatment and clinical
research center.

Patients Fourteen patients who met the criteria for
relapsing-remitting MS and major depressive disorder.

Main Outcome Measures Depression was assessed using the
Beck Depression Inventory. Interferon gamma production by peripheral blood
mononuclear cells was measured following stimulation with OKT3 or recombinant
human myelin oligodendrocyte glycoprotein (MOG). Variability in immune assays
was controlled using 8 nondepressed healthy subjects who were enrolled at times
corresponding with the enrollment of MS patients.

Results Results of the Beck Depression Inventory were
significantly related to IFN-gamma production stimulated with OKT3 or MOG at
baseline (P>=.03 for all). Level of depression, OKT3-stimulated IFN-gamma
production, and MOG-stimulated IFN-gamma production all declined significantly
over the 16-week treatment period (P>=.03 for all). Among controls,
there were no significant changes over time in OKT3- or MOG-stimulated IFN-gamma,
or in depression (P>=.25 for all).

Conclusions These findings suggest that the production of
the proinflammatory cytokine IFN-gamma by autoaggressive T cells in
relapsing-remitting MS is related to depression and that treatment of depression
may decrease IFN-gamma production. Thus, treatment of depression may provide a
novel disease-modifying therapeutic strategy as well as a symptomatic treatment
for patients with MS.